The proposed research involves the study of the amphipathic helix as a structural-functional unit of apolipoproteins. The lipid binding properties of a series of synthetic peptides have been compared to establish significant characteristics of the amphipathic helix. In comparison to apolipoprotein AI, our synthetic model amphipathic peptide demonstrated higher lipid affinity, based on carboxyfluroescein leakage studies. The analog peptide failed to demonstrate similar behavior as indicated by a series of studies. In addition, the model peptide displaced the protein component from HDL completely and most probably all of apolipoprotein C from VLDL. A longer twenty-one amino acid peptide has already been prepared and soon will be compared to the eighteen residue model peptide to determine the effect of peptide length on lipid affinity. We are presently in the process of preparing analogs of the eighteen model peptide, of varying hydrophobicity in order to determine the effect of hydrophobicity on lipid affinity. Upon conclusion of all these studies, a direct association of the important parameters of an amphipathic helix, i.e. charge distribution, length and hydrophobicity, will be made to its lipid binding properties.